Inflammation and reactive oxygen species as disease modifiers in epilepsy

Neuroinflammation and reactive oxygen and nitrogen species are rapidly induced in the brain after acute cerebral injuries that are associated with an enhanced risk for epilepsy in humans and related animal models. These phenomena reinforce each others and persist during epileptogenesis as well as during chronic spontaneous seizures. Anti-inflammatory and anti-oxidant drugs transiently administered either before, or shortly after the clinical onset of symptomatic epilepsy, similarly block the progression of spontaneous seizures, and may delay their onset. Moreover, neuroprotection and rescue of cognitive deficits are also observed in the treated animals. Therefore, although these treatments do not prevent epilepsy development, they offer clinically relevant disease-modification effects. These therapeutic effects are mediated by targeting molecular signaling pathways such as the IL-1β−IL-1 receptor type 1 and TLR4, P2X7 receptors, the transcriptional anti-oxidant factor Nrf2, while the therapeutic impact of COX-2 inhibition for reducing spontaneous seizures remains controversial.